The overall goal of this project is to develop a therapeutic method for targeted delivery of IL-4 to arthritic joints. Rheumatoid arthritis is an autoimmune disease characterized by progressive cartilage and bone erosion. Cytokines are important modulators of immune responses and IL-4 is an attractive cytokine for treating arthritis. Local administration of IL-4 has therapeutic effects in patients with moderate arthritis. However, the therapeutic efficacy of the cytokine is limited due to its toxicity. To improve the cytokine therapeutic effect, its concentration in a disease site has to be increased without causing undesirable side effects. The proposed method suppresses the biological activity of the administered cytokine until it reaches proximity of a target cell. The cytokine is then rendered active and concentrates in a disease site. The cytokine concentration in arthritic joints can reach levels that have desired therapeutic effects without systemic toxicity. This targeted delivery approach can be adapted for other cytokines and diseases and can be used as adjuvant to other treatments or stand alone. In Phase I we will develop the biological reagents and test them in vitro. We will use these reagents in Phase II in preclinical studies evaluating treatment of arthritis in animals.